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. 1997 Apr 15;99(8):1864–1872. doi: 10.1172/JCI119353

Posttranscriptional effect of insulin-like growth factor-I on interleukin-1beta-induced type II-secreted phospholipase A2 gene expression in rabbit articular chondrocytes.

C Jacques 1, G Béréziat 1, L Humbert 1, J L Olivier 1, M T Corvol 1, J Masliah 1, F Berenbaum 1
PMCID: PMC508010  PMID: 9109430

Abstract

Large amounts of type II-secreted phospholipase A2 (type II sPLA2) are secreted into inflammatory synovial fluid and they are believed to induce the synthesis of lipid mediators by articular chondrocytes. Preliminary experiments showed that insulin-like growth factor-I, which counteracts cartilage degradation in arthritis, inhibits interleukin-1beta-induced type II sPLA2 gene expression in rabbit articular chondrocytes (Berenbaum, F., G. Thomas, S. Poiraudeau, G. Bereziat, M.T. Corvol, and J. Masliah. 1994. FEBS Lett. 340: 51-55). The present study showed that IL-1beta induced the sustained synthesis of prostaglandin E2 and a parallel increase in type II sPLA2 gene expression (assessed by enzymatic activity and Northern blot analysis), but no increase in cytosolic PLA2 gene expression (assessed by Northern and Western blot analysis) or cytosolic PLA2 activity in rabbit articular chondrocytes. IGF-I inhibited both IL-1beta-stimulated PGE2 synthesis and type II sPLA2 gene expression, but had no effect on cytosolic PLA2 gene expression. Nuclear run-on experiments revealed that IL-1beta stimulated the transcription rate of type II sPLA2 gene, giving rise to long-lived mRNA in cells treated with actinomycin D. IGF-I did not affect transcription rate, suggesting that it acts as a post-transcriptional step. Sucrose density gradient analysis of the translation step showed no effect of IGF-I on the entry of type II sPLA2 mRNA into the polysomal pool or on its distribution into the various polysomal complexes, suggesting that IGF-I does not act on the translation of the mRNA. Lastly, IGF-I strongly decreased the half-life of IL-1beta-induced type II sPLA2 mRNA (from 92 to 12 h), suggesting that IGF-I destabilizes mRNA. These data demonstrate that IL-1beta stimulates the transcription rate of the type II sPLA2 gene and gives rise to a very stable mRNA. In contrast, IGF-I decreases the half-life of the type II sPLA2 message.

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Selected References

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  1. Angel J., Berenbaum F., Le Denmat C., Nevalainen T., Masliah J., Fournier C. Interleukin-1-induced prostaglandin E2 biosynthesis in human synovial cells involves the activation of cytosolic phospholipase A2 and cyclooxygenase-2. Eur J Biochem. 1994 Nov 15;226(1):125–131. doi: 10.1111/j.1432-1033.1994.tb20033.x. [DOI] [PubMed] [Google Scholar]
  2. Antras J., Lasnier F., Pairault J. Adipsin gene expression in 3T3-F442A adipocytes is posttranscriptionally down-regulated by retinoic acid. J Biol Chem. 1991 Jan 15;266(2):1157–1161. [PubMed] [Google Scholar]
  3. Atwater J. A., Wisdom R., Verma I. M. Regulated mRNA stability. Annu Rev Genet. 1990;24:519–541. doi: 10.1146/annurev.ge.24.120190.002511. [DOI] [PubMed] [Google Scholar]
  4. BLIGH E. G., DYER W. J. A rapid method of total lipid extraction and purification. Can J Biochem Physiol. 1959 Aug;37(8):911–917. doi: 10.1139/o59-099. [DOI] [PubMed] [Google Scholar]
  5. Barbu V., Dautry F. Northern blot normalization with a 28S rRNA oligonucleotide probe. Nucleic Acids Res. 1989 Sep 12;17(17):7115–7115. doi: 10.1093/nar/17.17.7115. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Bartoli F., Lin H. K., Ghomashchi F., Gelb M. H., Jain M. K., Apitz-Castro R. Tight binding inhibitors of 85-kDa phospholipase A2 but not 14-kDa phospholipase A2 inhibit release of free arachidonate in thrombin-stimulated human platelets. J Biol Chem. 1994 Jun 3;269(22):15625–15630. [PubMed] [Google Scholar]
  7. Berenbaum F., Jacques C., Thomas G., Corvol M. T., Béréziat G., Masliah J. Synergistic effect of interleukin-1 beta and tumor necrosis factor alpha on PGE2 production by articular chondrocytes does not involve PLA2 stimulation. Exp Cell Res. 1996 Feb 1;222(2):379–384. doi: 10.1006/excr.1996.0047. [DOI] [PubMed] [Google Scholar]
  8. Berenbaum F., Thomas G., Poiraudeau S., Béréziat G., Corvol M. T., Masliah J. Insulin-like growth factors counteract the effect of interleukin 1 beta on type II phospholipase A2 expression and arachidonic acid release by rabbit articular chondrocytes. FEBS Lett. 1994 Feb 28;340(1-2):51–55. doi: 10.1016/0014-5793(94)80171-1. [DOI] [PubMed] [Google Scholar]
  9. Bomalaski J. S., Lawton P., Browning J. L. Human extracellular recombinant phospholipase A2 induces an inflammatory response in rabbit joints. J Immunol. 1991 Jun 1;146(11):3904–3910. [PubMed] [Google Scholar]
  10. Bomsztyk K., Rooney J. W., Iwasaki T., Rachie N. A., Dower S. K., Sibley C. H. Evidence that interleukin-1 and phorbol esters activate NF-kappa B by different pathways: role of protein kinase C. Cell Regul. 1991 Apr;2(4):329–335. doi: 10.1091/mbc.2.4.329. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Bonaventure J., de La Tour B., Tsagris L., Eddie L. W., Tregear G., Corvol M. T. Effect of relaxin on the phenotype of collagens synthesized by cultured rabbit chondrocytes. Biochim Biophys Acta. 1988 Nov 18;972(2):209–220. doi: 10.1016/0167-4889(88)90119-x. [DOI] [PubMed] [Google Scholar]
  12. Chen X., Sparks J. D., Yao Z., Fisher E. A. Hepatic polysomes that contain apoprotein B mRNA have unusual physical properties. J Biol Chem. 1993 Oct 5;268(28):21007–21013. [PubMed] [Google Scholar]
  13. Chock S. P., Schmauder-Chock E. A., Cordella-Miele E., Miele L., Mukherjee A. B. The localization of phospholipase A2 in the secretory granule. Biochem J. 1994 Jun 15;300(Pt 3):619–622. doi: 10.1042/bj3000619. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Chomczynski P., Sacchi N. Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal Biochem. 1987 Apr;162(1):156–159. doi: 10.1006/abio.1987.9999. [DOI] [PubMed] [Google Scholar]
  15. Cirino G., Cicala C., Sorrentino L., Maiello F. M., Browning J. L. Recombinant secreted nonpancreatic phospholipase A2 induces a synovitis-like inflammation in the rat air pouch. J Rheumatol. 1994 May;21(5):824–829. [PubMed] [Google Scholar]
  16. Clark J. D., Lin L. L., Kriz R. W., Ramesha C. S., Sultzman L. A., Lin A. Y., Milona N., Knopf J. L. A novel arachidonic acid-selective cytosolic PLA2 contains a Ca(2+)-dependent translocation domain with homology to PKC and GAP. Cell. 1991 Jun 14;65(6):1043–1051. doi: 10.1016/0092-8674(91)90556-e. [DOI] [PubMed] [Google Scholar]
  17. Corvol M. T., Dumontier M. F., Rappaport R. Culture of chondrocytes from the proliferative zone of epiphyseal growth plate cartilage from prepubertal rabbits. Biomedicine. 1975 Apr 10;23(3):103–107. [PubMed] [Google Scholar]
  18. Dennis E. A. Diversity of group types, regulation, and function of phospholipase A2. J Biol Chem. 1994 May 6;269(18):13057–13060. [PubMed] [Google Scholar]
  19. Dessen P., Fondrat C., Valencien C., Mugnier C. BISANCE: a French service for access to biomolecular sequence databases. Comput Appl Biosci. 1990 Oct;6(4):355–356. doi: 10.1093/bioinformatics/6.4.355. [DOI] [PubMed] [Google Scholar]
  20. Doré S., Abribat T., Rousseau N., Brazeau P., Tardif G., DiBattista J. A., Cloutier J. M., Pelletier J. P., Martel-Pelletier J. Increased insulin-like growth factor 1 production by human osteoarthritic chondrocytes is not dependent on growth hormone action. Arthritis Rheum. 1995 Mar;38(3):413–419. doi: 10.1002/art.1780380319. [DOI] [PubMed] [Google Scholar]
  21. Fourcade O., Simon M. F., Viodé C., Rugani N., Leballe F., Ragab A., Fournié B., Sarda L., Chap H. Secretory phospholipase A2 generates the novel lipid mediator lysophosphatidic acid in membrane microvesicles shed from activated cells. Cell. 1995 Mar 24;80(6):919–927. doi: 10.1016/0092-8674(95)90295-3. [DOI] [PubMed] [Google Scholar]
  22. Hidi R., Vargaftig B. B., Touqui L. Increased synthesis and secretion of a 14-kDa phospholipase A2 by guinea pig alveolar macrophages. Dissociation from arachidonic acid liberation and modulation by dexamethasone. J Immunol. 1993 Nov 15;151(10):5613–5623. [PubMed] [Google Scholar]
  23. Jackson R. J. Cytoplasmic regulation of mRNA function: the importance of the 3' untranslated region. Cell. 1993 Jul 16;74(1):9–14. doi: 10.1016/0092-8674(93)90290-7. [DOI] [PubMed] [Google Scholar]
  24. Jansen J., van Buul-Offers S. C., Hoogerbrugge C. M., de Poorter T. L., Corvol M. T., Van den Brande J. L. Characterization of specific insulin-like growth factor (IGF)-I and IGF-II receptors on cultured rabbit articular chondrocyte membranes. J Endocrinol. 1989 Feb;120(2):245–249. doi: 10.1677/joe.0.1200245. [DOI] [PubMed] [Google Scholar]
  25. Kerr J. S., Stevens T. M., Davis G. L., McLaughlin J. A., Harris R. R. Effects of recombinant interleukin-1 beta on phospholipase A2 activity, phospholipase A2 mRNA levels, and eicosanoid formation in rabbit chondrocytes. Biochem Biophys Res Commun. 1989 Dec 29;165(3):1079–1084. doi: 10.1016/0006-291x(89)92712-5. [DOI] [PubMed] [Google Scholar]
  26. Komada M., Kudo I., Mizushima H., Kitamura N., Inoue K. Structure of cDNA coding for rat platelet phospholipase A2. J Biochem. 1989 Oct;106(4):545–547. doi: 10.1093/oxfordjournals.jbchem.a122890. [DOI] [PubMed] [Google Scholar]
  27. Kramer R. M., Hession C., Johansen B., Hayes G., McGray P., Chow E. P., Tizard R., Pepinsky R. B. Structure and properties of a human non-pancreatic phospholipase A2. J Biol Chem. 1989 Apr 5;264(10):5768–5775. [PubMed] [Google Scholar]
  28. Kudo I., Murakami M., Hara S., Inoue K. Mammalian non-pancreatic phospholipases A2. Biochim Biophys Acta. 1993 Nov 3;1170(3):217–231. doi: 10.1016/0005-2760(93)90003-r. [DOI] [PubMed] [Google Scholar]
  29. Lambeau G., Ancian P., Barhanin J., Lazdunski M. Cloning and expression of a membrane receptor for secretory phospholipases A2. J Biol Chem. 1994 Jan 21;269(3):1575–1578. [PubMed] [Google Scholar]
  30. Lyons-Giordano B., Davis G. L., Galbraith W., Pratta M. A., Arner E. C. Interleukin-1 beta stimulates phospholipase A2 mRNA synthesis in rabbit articular chondrocytes. Biochem Biophys Res Commun. 1989 Oct 16;164(1):488–495. doi: 10.1016/0006-291x(89)91746-4. [DOI] [PubMed] [Google Scholar]
  31. Marzluff W. F., Jr, Murphy E. C., Jr, Huang R. C. Transcription of the genes for 5S ribosomal RNA and transfer RNA in isolated mouse myeloma cell nuclei. Biochemistry. 1974 Aug 27;13(18):3689–3696. doi: 10.1021/bi00715a011. [DOI] [PubMed] [Google Scholar]
  32. McQuillan D. J., Handley C. J., Campbell M. A., Bolis S., Milway V. E., Herington A. C. Stimulation of proteoglycan biosynthesis by serum and insulin-like growth factor-I in cultured bovine articular cartilage. Biochem J. 1986 Dec 1;240(2):423–430. doi: 10.1042/bj2400423. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Morgan D. W., Anderson C. M., Meyers K. P. Recombinant human type II phospholipase A2 lacks edema producing activity in rat. Eur J Pharmacol. 1993 Apr 22;235(1):45–50. doi: 10.1016/0014-2999(93)90818-3. [DOI] [PubMed] [Google Scholar]
  34. Mounier C., Faili A., Vargaftig B. B., Bon C., Hatmi M. Secretory phospholipase A2 is not required for arachidonic acid liberation during platelet activation. Eur J Biochem. 1993 Aug 15;216(1):169–175. doi: 10.1111/j.1432-1033.1993.tb18129.x. [DOI] [PubMed] [Google Scholar]
  35. Murakami M., Kudo I., Inoue K. Eicosanoid generation from antigen-primed mast cells by extracellular mammalian 14-kDa group II phospholipase A2. FEBS Lett. 1991 Dec 9;294(3):247–251. doi: 10.1016/0014-5793(91)81440-j. [DOI] [PubMed] [Google Scholar]
  36. Murakami M., Kudo I., Nakamura H., Yokoyama Y., Mori H., Inoue K. Exacerbation of rat adjuvant arthritis by intradermal injection of purified mammalian 14-kDa group II phospholipase A2. FEBS Lett. 1990 Jul 30;268(1):113–116. doi: 10.1016/0014-5793(90)80986-s. [DOI] [PubMed] [Google Scholar]
  37. Murakami M., Kudo I., Suwa Y., Inoue K. Release of 14-kDa group-II phospholipase A2 from activated mast cells and its possible involvement in the regulation of the degranulation process. Eur J Biochem. 1992 Oct 1;209(1):257–265. doi: 10.1111/j.1432-1033.1992.tb17284.x. [DOI] [PubMed] [Google Scholar]
  38. Mühl H., Geiger T., Pignat W., Märki F., van den Bosch H., Cerletti N., Cox D., McMaster G., Vosbeck K., Pfeilschifter J. Transforming growth factors type-beta and dexamethasone attenuate group II phospholipase A2 gene expression by interleukin-1 and forskolin in rat mesangial cells. FEBS Lett. 1992 Apr 20;301(2):190–194. doi: 10.1016/0014-5793(92)81245-h. [DOI] [PubMed] [Google Scholar]
  39. Mühl H., Geiger T., Pignat W., Märki F., van den Bosch H., Vosbeck K., Pfeilschifter J. PDGF suppresses the activation of group II phospholipase A2 gene expression by interleukin 1 and forskolin in mesangial cells. FEBS Lett. 1991 Oct 21;291(2):249–252. doi: 10.1016/0014-5793(91)81295-j. [DOI] [PubMed] [Google Scholar]
  40. Nemenoff R. A., Winitz S., Qian N. X., Van Putten V., Johnson G. L., Heasley L. E. Phosphorylation and activation of a high molecular weight form of phospholipase A2 by p42 microtubule-associated protein 2 kinase and protein kinase C. J Biol Chem. 1993 Jan 25;268(3):1960–1964. [PubMed] [Google Scholar]
  41. Olivier J. L., Fan Q., Salvat C., Ziari M., Kong L., Mangeney M., Bereziat G. Positive and negative hepatic regulation of the human type II phospholipase A2 gene. Biochemistry. 1994 Jun 14;33(23):7134–7145. doi: 10.1021/bi00189a017. [DOI] [PubMed] [Google Scholar]
  42. Pause A., Belsham G. J., Gingras A. C., Donzé O., Lin T. A., Lawrence J. C., Jr, Sonenberg N. Insulin-dependent stimulation of protein synthesis by phosphorylation of a regulator of 5'-cap function. Nature. 1994 Oct 27;371(6500):762–767. doi: 10.1038/371762a0. [DOI] [PubMed] [Google Scholar]
  43. Pernas P., Masliah J., Olivier J. L., Salvat C., Rybkine T., Bereziat G. Type II phospholipase A2 recombinant overexpression enhances stimulated arachidonic acid release. Biochem Biophys Res Commun. 1991 Aug 15;178(3):1298–1305. doi: 10.1016/0006-291x(91)91035-b. [DOI] [PubMed] [Google Scholar]
  44. Pfeilschifter J., Schalkwijk C., Briner V. A., van den Bosch H. Cytokine-stimulated secretion of group II phospholipase A2 by rat mesangial cells. Its contribution to arachidonic acid release and prostaglandin synthesis by cultured rat glomerular cells. J Clin Invest. 1993 Nov;92(5):2516–2523. doi: 10.1172/JCI116860. [DOI] [PMC free article] [PubMed] [Google Scholar]
  45. Pruzanski W., Bogoch E., Katz A., Wloch M., Stefanski E., Grouix B., Sakotic G., Vadas P. Induction of release of secretory nonpancreatic phospholipase A2 from human articular chondrocytes. J Rheumatol. 1995 Nov;22(11):2114–2119. [PubMed] [Google Scholar]
  46. Radvanyi F., Jordan L., Russo-Marie F., Bon C. A sensitive and continuous fluorometric assay for phospholipase A2 using pyrene-labeled phospholipids in the presence of serum albumin. Anal Biochem. 1989 Feb 15;177(1):103–109. doi: 10.1016/0003-2697(89)90022-5. [DOI] [PubMed] [Google Scholar]
  47. Reddy S. T., Herschman H. R. Transcellular prostaglandin production following mast cell activation is mediated by proximal secretory phospholipase A2 and distal prostaglandin synthase 1. J Biol Chem. 1996 Jan 5;271(1):186–191. doi: 10.1074/jbc.271.1.186. [DOI] [PubMed] [Google Scholar]
  48. Riendeau D., Guay J., Weech P. K., Laliberté F., Yergey J., Li C., Desmarais S., Perrier H., Liu S., Nicoll-Griffith D. Arachidonyl trifluoromethyl ketone, a potent inhibitor of 85-kDa phospholipase A2, blocks production of arachidonate and 12-hydroxyeicosatetraenoic acid by calcium ionophore-challenged platelets. J Biol Chem. 1994 Jun 3;269(22):15619–15624. [PubMed] [Google Scholar]
  49. Rosenthal M. D., Gordon M. N., Buescher E. S., Slusser J. H., Harris L. K., Franson R. C. Human neutrophils store type II 14-kDa phospholipase A2 in granules and secrete active enzyme in response to soluble stimuli. Biochem Biophys Res Commun. 1995 Mar 17;208(2):650–656. doi: 10.1006/bbrc.1995.1388. [DOI] [PubMed] [Google Scholar]
  50. Schalkwijk C., Pfeilschifter J., Märki F., van den Bosch H. Interleukin-1 beta- and forskolin-induced synthesis and secretion of group II phospholipase A2 and prostaglandin E2 in rat mesangial cells is prevented by transforming growth factor-beta 2. J Biol Chem. 1992 May 5;267(13):8846–8851. [PubMed] [Google Scholar]
  51. Schoenle E., Zapf J., Humbel R. E., Froesch E. R. Insulin-like growth factor I stimulates growth in hypophysectomized rats. Nature. 1982 Mar 18;296(5854):252–253. doi: 10.1038/296252a0. [DOI] [PubMed] [Google Scholar]
  52. Seilhamer J. J., Pruzanski W., Vadas P., Plant S., Miller J. A., Kloss J., Johnson L. K. Cloning and recombinant expression of phospholipase A2 present in rheumatoid arthritic synovial fluid. J Biol Chem. 1989 Apr 5;264(10):5335–5338. [PubMed] [Google Scholar]
  53. Seilhamer J. J., Randall T. L., Yamanaka M., Johnson L. K. Pancreatic phospholipase A2: isolation of the human gene and cDNAs from porcine pancreas and human lung. DNA. 1986 Dec;5(6):519–527. doi: 10.1089/dna.1.1986.5.519. [DOI] [PubMed] [Google Scholar]
  54. Sharp J. D., White D. L., Chiou X. G., Goodson T., Gamboa G. C., McClure D., Burgett S., Hoskins J., Skatrud P. L., Sportsman J. R. Molecular cloning and expression of human Ca(2+)-sensitive cytosolic phospholipase A2. J Biol Chem. 1991 Aug 15;266(23):14850–14853. [PubMed] [Google Scholar]
  55. Suga H., Murakami M., Kudo I., Inoue K. Participation in cellular prostaglandin synthesis of type-II phospholipase A2 secreted and anchored on cell-surface heparan sulfate proteoglycan. Eur J Biochem. 1993 Dec 15;218(3):807–813. doi: 10.1111/j.1432-1033.1993.tb18435.x. [DOI] [PubMed] [Google Scholar]
  56. Vadas P., Pruzanski W., Kim J., Fornasier V. The proinflammatory effect of intra-articular injection of soluble human and venom phospholipase A2. Am J Pathol. 1989 Apr;134(4):807–811. [PMC free article] [PubMed] [Google Scholar]
  57. Yoza B. K., Brooks J. W., Mizel S. B. Induction of AP-1 transcription factor components during T-cell activation by interleukin 1 and phorbol esters. Cell Growth Differ. 1992 Oct;3(10):677–684. [PubMed] [Google Scholar]
  58. van den Bosch H., van Deenen L. L. Chemical structure and biochemical significance of lysolecithins from rat liver. Biochim Biophys Acta. 1965 Oct 4;106(2):326–337. doi: 10.1016/0005-2760(65)90041-x. [DOI] [PubMed] [Google Scholar]

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